Contrast from rotating frame relaxation by adiabatic pulses

ABSTRACT

This document discusses, among other things, a system and method for modulating transverse and longitudinal relaxation time contrast in a rotating frame based on a train of radio frequency pulses.

CROSS-REFERENCE TO RELATED APPLICATIONS

This document claims the benefit of priority, under 35 U.S.C. § 119(e),to Shalom Michaeli et. al, U.S. Provisional Patent Application Ser. No.60/616,257, entitled “TRANSVERSE AND LONGITUDINAL RELAXATION TIMECONTRAST IN THE ROTATING FRAME GENERATED BY ADIABATIC RF PULSES,” filedon Oct. 6, 2004, which is incorporated herein by reference.

GOVERNMENT INTEREST

This work was supported by NIH grants CA92004, RR08079, NS 40801, EB00422, the Keck Foundation, the MIND Institute, the National Foundationfor Functional Brain Imaging and the US Department of Energy. The UnitedStates government has certain rights in the technology disclosed herein.

TECHNICAL FIELD

This document pertains generally to magnetic resonance spectroscopy, andmore particularly, but not by way of limitation, to contrast fromrotating frame relaxation by adiabatic pulses.

BACKGROUND

Relaxation is a measure of the differences in the way that a molecule,such as water for example, relaxes following excitation. The relaxationrate constants of the spins located in different environments aredifferent. A magnetic resonance image can be generated that is sensitiveto the density of the water but in different tissues, the waterconcentration (or the density) changes little.

Relaxation provides a measure as to the environment in which the watermolecule is located. For example, a water molecule excited by a radiofrequency (RF) pulse gives energy off to the environment by interactingwith other magnetic dipoles.

Among other factors, the rate constant depends on interaction betweennearby molecules in the environment.

Longitudinal relaxation is characterized by time constant T₁, e.g. timeconstant at which a disturbed magnetic vector returns to alignment witha static magnetic field.

Transverse relaxation, or spin-spin relaxation, is characterized by atime constant T₂ at which the magnetization vector dephase in the planeperpendicular to the static magnetic field. The plane perpendicular tothe static magnetic field is called the transverse plane.

Current methods for assessing relaxation and generating contrast in therotating frame are inadequate.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, which are not necessarily drawn to scale, like numeralsdescribe substantially similar components throughout the several views.Like numerals having different letter suffixes represent differentinstances of substantially similar components. The drawings illustrategenerally, by way of example, but not by way of limitation, variousembodiments discussed in the present document.

FIGS. 1A and 1B include schematic representations of the fully adiabaticCP and DSE pulse sequences.

FIGS. 2A-2E illustrate experimental image results for different pulsetrains.

FIGS. 3A-3D illustrate apparent T₂ ^(†) data generated from thesingle-subject measurements.

FIGS. 4A and 4B illustrate averaged calculated T₂ ^(†) time constants at4T (6 individuals) and at 7T (5 individuals) as a function of τ_(cp) andthe superimposed simulations.

FIGS. 5A-5F illustrate a schematic representation of the adiabatic pulsesequence used for adiabatic T_(1ρ) measurements and image results.

FIGS. 6A and 6B illustrate calculated longitudinal relaxation rateconstants during different pulses as a function of the rotationalcorrelation time (τ_(c)).

FIGS. 7A and 7B illustrate the rotating frame of reference.

FIGS. 8A and 8B illustrate exemplary pulse modulation functions.

FIG. 9 illustrates theoretical comparison between selected relaxationmechanisms during adiabatic pulses.

FIG. 10 includes a block diagram of an exemplary magnetic resonancesystem.

FIG. 11 illustrates an exemplary method according to the present subjectmatter.

DETAILED DESCRIPTION

The following detailed description includes references to theaccompanying drawings, which form a part of the detailed description.The drawings show, by way of illustration, specific embodiments in whichthe invention may be practiced. These embodiments, which are alsoreferred to herein as “examples,” are described in enough detail toenable those skilled in the art to practice the invention. Theembodiments may be combined, other embodiments may be utilized, orstructural, logical and electrical changes may be made without departingfrom the scope of the present invention. The following detaileddescription is, therefore, not to be taken in a limiting sense, and thescope of the present invention is defined by the appended claims andtheir equivalents.

In this document, the terms “a” or “an” are used, as is common in patentdocuments, to include one or more than one. In this document, the term“or” is used to refer to a nonexclusive or, unless otherwise indicated.Furthermore, all publications, patents, and patent documents referred toin this document are incorporated by reference herein in their entirety,as though individually incorporated by reference. In the event ofinconsistent usages between this document and those documents soincorporated by reference, the usage in the incorporated reference(s)should be considered supplementary to that of this document; forirreconcilable inconsistencies, the usage in this document controls.

Transverse relaxation in the rotating frame (T_(2ρ)) is believed to bethe dominant relaxation mechanism during an adiabatic Carr-Purcell (CP)spin-echo pulse sequence when no delays are used between pulses in theCP train. The exchange-induced and dipolar interaction contributions(T_(2ρ,ex) and T_(2ρ,dd)) depend on the modulation functions of theadiabatic pulses used. Adiabatic pulses having different modulationfunctions can be used to generate T_(2ρ) contrast in images. In oneexample, images of the human occipital lobe are generated at magneticfield of 4T. T_(2ρ) time constants can be measured using an adiabatic CPpulse sequence followed by an imaging readout. In one example, adiabaticfull passage pulses of the hyperbolic secant HSn (n=1 or 4) familyhaving significantly different amplitude modulation and frequencymodulation functions were used with no time delays between pulses. Adynamic averaging (DA) mechanism (e.g. chemical exchange and diffusionin the locally different magnetic susceptibilities) provides a partialexplanation to describe differences in brain tissue water proton T_(2ρ)time constants. Measurements of the apparent relaxation time constants(T₂ ^(†)) of brain tissue water as a function of the time betweencenters of pulses (τ_(cp)) at 4T and 7T permits separation of the DAcontribution from that of dipolar relaxation. In various examples, amethod is presented for assessing T_(2ρ) relaxation influenced by DA intissue, and also means to generate T_(2ρ) contrast in MRI.

Chemical exchange (CE) between spins located at different magnetic siteswith different chemical shifts or diffusion of spins through magneticfield inhomogeneities contribute to transverse relaxation in vivo.Collectively, these relaxation processes are referred to here as dynamicaveraging (DA). Dephasing due to molecular diffusion in microscopicsusceptibility gradients or CE occurs for example around paramagneticproteins, organelles, and capillaries. The apparent transverserelaxation time constant (T₂ ^(†)) decrease due to DA can be used for invivo quantification of brain iron because of its relevance to severalneurodegenerative disorders including Parkinson's and Alzheimer'sdisease as well as for understanding the mechanisms of blood oxygenationlevel dependent (BOLD) contrast. The model of T₂ ^(†) decrease due to DAdescribes transverse relaxation induced by paramagnetic complexes andalso relaxation in blood.

Proton relaxation studies are motivated by the importance ofrelaxation-based contrast in clinical applications of MR imaging andspectroscopy. An exemplary contrast method is based on the fullyadiabatic Carr-Purcell (CP) technique. The dependence of the T₂ ^(†)values of human brain tissue water and cerebral metaboliteN-acetylaspartate and total creatine proton signals on the temporalspacing (τ_(cp)) of pulses in the CP train at high magnetic fields (4Tand 7T) may reflect DA. In one example, relaxation techniques were usedto generate contrast for monitoring response to gene therapy in ratglioma and for investigating the acute cerebral ischaemia in rats.

Rotating frame transverse relaxation (time constant, T_(2ρ)) dominatesduring adiabatic pulses used in a CP pulse sequence. A theory ispresented for the two-site-exchange (2SX)-induced T_(2ρ) contribution(T_(2ρ,ex)) from a system of otherwise identical spins with a nonzerochemical shift difference (δω≠0) in the fast chemical exchange limit(FXL). T_(2ρ,ex) and the T_(2ρ) contribution from dipolar interactions(T_(2ρ,dd)) with rotational correlation times τ_(c)>10⁻⁹s duringadiabatic pulses depends on the frequency modulation and amplitudemodulation functions used for the adiabatic pulses. T_(2ρ) measurementsusing adiabatic full-passage (AFP) pulses, such as hyperbolic secant HSn(n=1 or 4) pulses provides a method for determining chemical exchangerate constants. The present adiabatic CP method generates tissuecontrast originating in T_(2ρ) mechanisms.

T_(2ρ) contrast in human brain tissue ¹H₂O MRI is generated by using AFPHS1 and HS4 pulses. Theoretical formalisms for T_(2ρ,ex) and T_(2ρ,dd)can be used to quantify the observed contrast. In one example, T₂ ^(†)measurements of water in brain tissue are generated as a function of thetemporal spacing, τ_(cp), of HSn pulses in the CP pulse sequence at 4Tand 7T field strengths.

Consider first the relaxations during the interpulse time intervals(τ_(ip)) in an adiabatic CP pulse sequence and during the AFP pulses.First, relaxation during the adiabatic pulses is described.

Transverse Relaxations during the Adiabatic Pulses

During AFP pulses in a CP train, the transverse relaxation is dominatedby T_(2ρ). Because the effective magnetic field, ω_(eff)(t), is timedependent during the adiabatic rotation, T_(2ρ) is also time dependentand thus is a function of the pulse modulation functions, ω₁(t) andω_(RF)(t). Here, ω₁(t) is the time-dependent RF amplitude and ω_(RF)(t)is time-dependent frequency of the pulse in rad/s. The amplitude of HSnpulses are given by:ω₁(t)=ω₁ ^(max)sech[β[2t/T _(p)−1]^(n)],  Eq. 1where t∈[0, T_(p)], β is a truncation factor (sech(β)=0.01), ω₁ ^(max)is the maximum value of ω₁(t) in rad/s, T_(p) is the pulse duration, andn=1 and 4 for HS1 and HS4 pulses, respectively. As n gets larger, theamplitude-modulation functions of the HSn pulses become flatter and timeevolution of magnetization significantly changes with the change of n.With respect to the carrier frequency ω_(c) (the center frequency in thebandwidth of interest), the frequency modulation for HS1 pulse is givenby:ω_(RF)(t)−ω_(c) =A tan h[β[2t/T _(p)−1]],  Eq. 2

and for the HS4 pulse is given by:

$\begin{matrix}{{{{\omega_{RF}(t)} - \omega_{c}} = {A{\int_{0}^{t}{\sec\;{h^{2}\left( {\beta\left( {{2{t^{\prime}/T_{p}}} - 1} \right)}^{4} \right)}{\mathbb{d}t^{\prime}}}}}},} & {{Eq}.\mspace{14mu} 3}\end{matrix}$

where A is the amplitude of the frequency sweep in rad/s. During AFPpulses, ω_(eff)(t) changes its orientation at the instantaneous angularvelocity, dα(t)/dt, with:

$\begin{matrix}{{{\alpha(t)} = {\tan^{- 1}\left( \frac{\omega_{1}(t)}{\Delta\;{\omega(t)}} \right)}},} & {{Eq}.\mspace{14mu} 4}\end{matrix}$

where Δω(t)=(ω₀−ω_(RF)(t)) and ω₀ is the Larmor frequency. The effectivefield during an adiabatic pulse is given by:ω_(eff)(t)=√{square root over (ω₁ ²(t)+Δω²(t))}{square root over (ω₁²(t)+Δω²(t))}.  Eq. 5

For a system of two equivalent nuclei in a single site, theinstantaneous rotating frame transverse relaxation rate constant due todipolar interactions is given by:

$\begin{matrix}\begin{matrix}{R_{{2\rho},{dd}} = {\frac{1}{\left( {40k_{dd}} \right)}\left\lbrack {{3\left( {{3\cos^{2}\alpha} - 1} \right)^{2}} + \frac{30\;\sin^{2}\alpha\;\cos^{2}\alpha}{1 + {\omega_{eff}^{2}\tau_{c}^{2}}} +} \right.}} \\\left. {\frac{3\;\sin^{4}\alpha}{1 + {4\omega_{eff}^{2}\tau_{c}^{2}}} + \frac{\left( {20 - {6\sin^{2}\alpha}} \right)}{1 + {\omega_{0}^{2}\tau_{c}^{2}}} + \frac{\left( {8 + {12\;\sin^{2}\alpha}} \right)}{1 + {4\omega_{0}^{2}\tau_{c}^{2}}}} \right\rbrack\end{matrix} & {{Eq}.\mspace{14mu} 6}\end{matrix}$

where

$\frac{1}{k_{dd}} = {2{I\left( {I + 1} \right)}\hslash^{2}\gamma^{4}r^{- 6}r^{- 6}{\tau_{c}.}}$Here r is the inter-nuclear distance and h is Planck's constant. Eq. 6can be used to calculate R_(2ρ,dd) during AFP pulses.

The rotating frame 2SX transverse relaxation for spin populations withδω≠0 (the anisochronous mechanism) can be derived. The instantaneousexchange-induced transverse relaxation rate constant in the FXL (τ_(ex)⁻¹>>δω) during the adiabatic pulses can be approximated as in Equation7:R _(2ρ,ex) =P _(A) P _(B)(δω)² cos²ατ_(ex),  Eq. 7where P_(A) and P_(B) are the fractional spin populations at sites A andB, and τ_(ex), is the correlation time for exchange (≡(τ_(A) ⁻¹+τ_(B)⁻¹)⁻¹). Note that R_(2ρ,ex) is single-valued only in the FXL.

A possible mechanism of the relaxations in tissue is CE between spinswith δω=0 (the isochronous case). This situation can be described forfree precession. For the 2SX case (between site A and site B) in theslow and intermediate exchange regimes, the signal intensity (SI) decayis described by biexponentiality (e.g., the sum of two exponentialfunctions: the coefficients are equal to the populations of sites A andB and the relaxation rate constants equal to (1/T_(2A)+1/τ_(A)) and(1/T_(2B)+1/τ_(B)), when T_(2A)≠T_(2B), and when the system is in theslow-exchange-limit, SXL). Here T_(2A) and T_(2B) are the transverserelaxation rate constants of the sites A and B in the absence ofchemical exchange. In this case, the FXL obtains only if the rateconstant characterizing the exchange kinetics, τ_(ex) ⁻¹, is alsosufficiently greater than the transverse relaxographic shutter-speed,|R_(2A)-R_(2B)|, where R_(2A)≡T_(2A) ⁻¹ and R_(2B)≡T_(2B) ⁻¹. In theFXL, the relaxation is governed by the monoexponential decay functionwith the relaxation rate constant:R ₂ =R _(2A) P _(A) +R _(2B) P _(B)  Eq. 8

Transverse relaxation rate constants R_(2A,B) denote relaxation otherthan CE such as dipolar interactions or cross-relaxations. Under RFirradiation, transverse relaxation due to cross-relaxations differs fromthe relaxation during free precession.

To calculate the average effective relaxation rate constant R _(2ρ)during an AFP pulse of length T_(p), all instantaneous contributionsduring the pulse are taken into account and the average relaxation rateconstant is determined by:

$\begin{matrix}{{\overset{\_}{R}\;}_{2\;\rho} = {{\frac{1}{T_{p}}{\int_{0}^{T_{p}}{{R_{{2\rho},{ex}}(t)}{\mathbb{d}t}}}} + {\frac{1}{T}{\int_{0}^{T_{p}}{{R_{{2\rho},{dd}}(t)}{{\mathbb{d}t}.}}}}}} & {{Eq}.\mspace{14mu} 9}\end{matrix}$

Theory predicts both the R_(2ρ,ex) and R_(2ρ,dd) rate constants to bedependent on the choice of amplitude modulation and frequency modulationfunctions for the adiabatic pulses via their α- and ω_(eff)dependencies.

Transverse Relaxations during the Interpulse Time Intervals

Relaxation during the interpulse time interval τ_(ip) is independent ofthe RF pulse parameters. The Luz-Meiboom CE theory, derived originallyin the Redfield limit, that describes the T₂ ^(†) decrease during the CPpulse sequence caused by CE between spins with different chemical shiftsδω, e.g., the anisochronous 2SX mechanism, was generalized to include adiffusion process. The transverse relaxation rate constant is given by:

$\begin{matrix}{R_{2,{DA}} = {\left( {\delta\;\omega} \right)^{2}P_{A}P_{B}\tau\left\{ {1 - {\left( {2\;{\tau/\tau_{ip}}} \right)\tan\;{h\left( \frac{\tau_{ip}}{2\tau} \right)}}} \right\}}} & {{Eq}.\mspace{14mu} 10}\end{matrix}$

Here τ=τ_(ex) or τ_(d), where τ_(d) is diffusion correlation time. WhenDA is not the only relaxation mechanism and additional relaxationpathways are operative, the relaxation rate constant is given by:R ₂ =R _(2,DA) +R ₂ ⁰  Eq. 11

Here, R₂ ⁰ describes the other relaxation mechanisms, such as dipolarinteraction or cross-relaxation. This theory allows determination of theτ, P_(A)P_(B)(δω)², and R_(2,DA) values. Because R_(2ρ,dd) is virtuallyindependent of magnetic field strength between 4T and 7T and R_(2,DA) issignificantly magnetic field strength dependent, measurements of thetransverse relaxation rate constants at different static magnetic fieldstrengths allows separation of the R_(2,DA) and R₂ ⁰ contributions toR₂.

Transverse Relaxations during the Entire Fully Adiabatic CP PulseSequence

Signal intensity decay during the adiabatic CP pulse sequence can bedescribed by the exponential decay functions during the pulses andduring the interpulse time intervals with the rate constants R_(2ρ)(t)and R₂, respectively:SI(n)=S ₀exp(− R _(2ρ) mT _(p))exp(−R ₂ mτ _(ip)),  Eq. 12

where m is a number of pulses in the adiabatic CP train andτ_(ip)=τ_(cp)−T_(p). From Eq. 12 the general expression for therelaxation rate constant during the adiabatic CP pulse sequence can bederived and expressed as:

$\begin{matrix}{R_{2}^{\dagger} = {{\left\{ {{\overset{\_}{R}}_{2\rho} - R_{2}} \right\}\frac{T_{p}}{\tau_{cp}}} + {R_{2}.}}} & {{Eq}.\mspace{14mu} 13}\end{matrix}$

Eq. 13 predicts that with no time delays between adiabatic pulses (i.e.,τ_(cp)=T_(p)) relaxation is governed by T_(2ρ) relaxation.

EXAMPLE

In one example, MRI studies were performed on healthy volunteers usinginstruments having Varian Unity INOVA consoles (Varian Associates, CA,USA) interfaced to a 90 cm bore 4T magnet (OMT, Inc., Oxon, UK) and to a90 cm bore 7T magnet (Magnex Scientific, UK). ¹H quadrature surfacecoils consisting of two geometrically decoupled turns (each 7 cm indiameter) were used for the measurements. T_(2ρ) and T₂ ^(†) images weremeasured with a segmented spiral readout, using (0.7 mm)² in-planeresolution, FOV=(18 cm)², 256² matrix, 8 segments, acquisition time(AT)=35 ms, and thickness=3 mm. Shimming was performed with a fullyadiabatic version of the fast automatic shimming technique by mappingalong projections, FASTMAP. Before the excitation pulse in thesequences, the fat signal at 1.3 ppm was suppressed by variable-power RFpulses with optimized relaxation delays, VAPOR. Two dummy scans wereused to achieve a steady state prior to data collection.

T_(2ρ) measurements were performed using variable numbers of HS1 or HS4pulses in the CP-train of the fully adiabatic pulse sequence, denotedCP^(HS1) and CP^(HS4), respectively (FIG. 1A). In the figure, selectiongradients and the spiral readout are not shown and the segment whichremains constant during T₂ measurements is denoted by t_(SL).

Each AFP pulse had an adiabaticity factor R equal to 20 (≡AT_(p)/π) withT_(p) set to 3 ms. The RF field amplitude ω₁ ^(max)/2π=2.5 kHz in allmeasurements. For the T_(2ρ) measurements, five subjects were scannedwith no delays between AFP pulses in the CP-train. In one example,T_(2ρ) measurements, T₂ ^(†) were measured with a double spin echo (DSE)pulse sequence (FIG. 1B), using the same TE values in both pulsesequences. In the DSE pulse sequence, two HS1 pulses were used prior toslice-selection, and various TE values were obtained by incrementing thetime between centers of the pulses, τ_(DSE). In the CP pulse sequence,various echo times were achieved by incrementing the number of pulses inthe CP-train with pulse phases set according to MLEV-4. Slice-selectionwas performed with two HS1 pulses applied in the presence of sliceselection gradients, and non-selective excitation was performed with anadiabatic half-passage (AHP) pulse. TE was varied (five TE values)between 22.2 and 72.2 ms, and TR=7 s was used. The RF energy depositedby CP train varied with the number of AFP pulses in the CP train and waskept below the FDA limit. T_(2ρ)- and T₂ ^(†)-maps from thesemeasurements were generated using the MATLAB software package (MATLAB6.1, Mathworks, MA), fitting the signal intensities to a monoexponentialdecay.

The τ_(cp) dependence of the T₂ ^(†) time constants at 4T (6 subjects)and 7T (5 subjects) was investigated using the CP^(HS1) pulse sequence.The length of the CP train was incremented keeping τ_(cp) constantthroughout the sequence. Because TR of the pulse sequence was constantduring the acquisition and TE was varied significantly when themeasurements were performed with long τ_(cp), the longitudinalrelaxation process was also taken into account. Possible contaminationby CSF can also influence the measurements of T₂ ^(†). Thus, theestimations of T₂ ^(†) were performed using a bi-exponential decayfunction:SI=A ₁exp(−TE/T ₂ ^(†))+A ₂exp(−TE/T _(L)).  Eq. 14

Here T_(L) spans the values of the transverse relaxation time constantsof CSF ¹H₂O and includes the longitudinal relaxation time constant T₁,of the brain tissue ¹H₂O. To estimate the variations of the fastcomponent of the bi-exponential decay (attributed to the T₂ ^(†) ofbrain tissue) with the change of the T_(L), the assumed relaxation timeconstant T_(L) was varied in the range 0.5-2.5 s. Within the range ofT_(L) examined, the average change of the T₂ ^(†) of brain tissue waswithin ±3.3% and the estimation of the δω varied within 2%.

FIGS. 2A-2E illustrate images including (2A) using CP^(HS1), (2B)CP^(HS4), (2C) and DSE images detected at TE=72.2 ms at 4T using spiralreadout. FIG. 2D illustrates a relative difference image, generated bysubtracting the CP^(HS1) image of FIG. 2A from the CP^(HS4) image ofFIG. 2B and then normalizing to the CP^(HS1) image. FIG. 2E illustratesa relative difference image, generated by subtracting the DSE image ofFIG. 2C from the CP^(HS1) image of FIG. 2A and then normalizing to theDSE image.

In particular, FIGS. 2A and 2B show coronal high-resolution imagesacquired at 4T from the occipital lobe of a representative subject,using CP pulse sequences with segmented spiral readout. Images wereacquired at TE=72.2 ms. Measurements were performed using HS4 (FIG. 2A)and HS1 (FIG. 2B) AFP pulses in the CP train. Because no delays betweenpulses were used, the relaxation was governed solely by T_(2ρ)processes. In FIG. 2C, the image acquired with the DSE pulse sequence(FIG. 1B) at TE=72.2 ms is shown. Relative difference images arepresented in FIGS. 2D and 2E. The image in FIG. 2D was obtained bysubtracting the CP^(HS1) image from the CP^(HS4) image and thennormalizing by the CP^(HS1)image. This difference indicates change inthe T_(2ρ) time constants due to the difference in the modulationfunctions of the AFP pulses used and reveals contrast generated solelyby T_(2ρ) relaxation. The image shown in FIG. 2E was obtained bysubtracting the DSE image from the CP^(HS1) image and then normalizingto the DSE image. This image contains contributions from both T_(2ρ) andT₂ (free precession transverse relaxation time constant during theinterpulse time intervals). Because of the simultaneous contribution ofrelaxation mechanisms that are differently weighted, the interpretationof contrast observed in FIG. 2E is more complicated than that in FIG.2D, and data analysis requires separate considerations of T_(2ρ) duringthe AFP pulses and T₂ during the free precession periods τ_(ip).

When the interpulse time intervals are varied to achieve the differentTEs with a constant number of AFP pulses, the T_(2ρ) relaxation imposesa constant weighting on the T₂ ^(†) measurements. This is also the casewith the DSE measurements. On the other hand, when T₂ ^(†)s are measuredwith the adiabatic CP pulse sequence having different τ_(cp) values andincrementing the number of pulses in the train, both relaxation pathways(e.g. T_(2ρ) and relaxation during free precession) contribute to themeasurements of T₂ ^(†).

T_(2ρ) and T₂ ^(†) maps from the same region of interest from singlesubject measurements are presented in FIGS. 3A, 3B and 3C. Inparticular, FIGS. 3A-3D illustrate T₂ ^(†)-maps generated from thesingle-subject measurements, detected with the (3A) DSE, (3B) CP^(HS1)and (3C) CP^(HS4) pulse sequences. FIG. 3D illustrates the T₂ ^(†) andT_(2ρ) relaxograms of a human brain image slice in the occipital lobe,generated from T₂ ^(†) and T_(2ρ) maps. T_(2ρ) images were obtained withno time delays between AFP in the CP pulse train. T₂ ^(†) images weremeasured with the DSE pulse sequence using a variable interpulse timeinterval.

The averaged intersubject results (MEAN±SD) of the T_(2ρ) measurementsfrom brain tissue regions are summarized in Table 1. Inspection of thistable reveals an increase in the T_(2ρ) measured when HS4 versus HS1pulses were used (p<0.03), with a ratio ofT_(2ρ)(CP^(HS4))/T_(2ρ)(CP^(HS1))=1.18 (multisubject data, n=5, Table1). For exchange-induced T_(2ρ,ex) obtained from the anisochronouswater/ethanol mixture with CP^(HS1) and CP^(HS4) pulse sequences, theratio T_(2ρ,ex)(CP^(HS4))/T_(2ρ,ex)(CP^(HS1)) was ˜1.5 when using thesame RF amplitude (ω₁ ^(max)/2π=2.5 kHz). A value ofT_(2ρ)(CP^(HS4))/T_(2ρ)(CP^(HS1))=1.18 measured here suggests thatrelaxation pathways other than the anisochronous DA must contribute to^(l)H₂O transverse relaxation in the brain.

TABLE 1 Averaged calculated T_(2ρ) (detected with CP^(HS1) and CP^(HS4))and T₂ ^(†) (detected with DSE) time constants of brain tissue at 4TPulse Sequences CP^(HS1) CP^(HS4) DSE CP^(HS4)/CP^(HS1) CP^(HS1)/DSET_(2ρ), T₂ ^(†) 72.8 ± 3.1^(a) 86 ± 3.4^(b) 59.2 ± 2.4^(b) 1.18 1.23^(a)Significant difference between CP^(HS1) and CP^(HS4) (p < 0.03,two-tailed). ^(b)Significant difference between CP^(HS1) and DSE (p <0.01, two-tailed).

T₂ ^(†) measurements as a function of τ_(cp) in the CP pulse sequencewas performed at 4T and 7T as illustrated in FIGS. 4A and 4B. For thesemeasurements, the CP^(HS1) pulse sequence was used. FIGS. 4A and 4B showplots of the T₂ ^(†) values (MEAN±SD) obtained in these measurements.The T₂ ^(†) values measured at 7T were smaller than those at 4T (p<0.01,two-tailed). T₂ ^(†) dependence on τ_(cp) was observed with τ_(cp)<12ms. With longer τ_(cp) values, the T₂ ^(†) time constants wereindependent of τ_(cp) (no significant difference, p>0.704).

In particular, FIG. 4A illustrates averaged calculated T₂ ^(†) timeconstants at 4T (for 6 individuals) and FIG. 4B illustrates results at7T (for 5 individuals) as a function of τ_(cp) and the superimposedsimulations (solid line) based on Eqs. 10, 11, 13. Errors representstandard deviations.

Fitting of the experimental data measured in human brain at 4T and 7Tusing Eqs. 10 and 13 yielded: δω(7T)/δω(4T)≈1.07. However, linearincrease of δω with magnetic field strength (a factor of 1.75 here) isrequired by the anisochronous DA model (Eq. 10). Therefore, this resultindicates that, in addition to anisochronous DA, other mechanismscontribute to transverse relaxation of brain ¹H₂O and these should beconsidered during the adiabatic CP pulse sequence. A likely possibilityis the dipolar interaction mechanism. Thus, assume that R_(2,dd)=R₂ ⁰.Fitting to the experimental data was obtained using R_(2ρ,dd)=6.0±0.4s⁻¹, with Eqs. 10, 11, 13 and the ratio δω(7T)/δω(4T)=1.59±0.25 (FIGS.4A and 4B). Other parameters obtained from the fitting were:τ_(ex)=1.05±0.15 ms, and P_(A)P_(B)(δω)²=(12.0±0.75)×10³(rad/s)² at 4T.For the dipolar interaction between identical spins, R_(2ρ,dd)≈6.0 s⁻¹corresponds to the correlation time τ_(c)≈1.1×10⁻¹⁰ s. Calculationsperformed using Eq. 6 (using r=1.58 Å for water) show that, for thiscorrelation time, R_(2ρ,dd) should be essentially independent of ω₀between 170 and 300 MHz. Moreover, it can be seen that, using Eqs. 6 and9 and τ_(c)=1.1×10⁻¹⁰ s, the dependence of R_(2ρ,dd) on the AFPmodulation functions is small. Thus, it was assumed that, both at 4T and7T, the same apparent dipolar relaxation rate constant contributes tothe CP^(HS1) and CP^(HS4) measurements. Water in the brain ischaracterized by different τ_(c) values corresponding to different waterenvironments, such as hydrated myelin sheet, cytoplasm or CSF. AlthoughT_(2ρ) contrast in brain ¹H₂O is expected to be sensitive to large watercorrelation times τ_(c)>10⁻⁹ s, such a contribution was found to beinsignificant.

In one example, the same parameters obtained from the measurements of T₂^(†) dependence on τ_(cp) in the adiabatic CP pulse sequence at 4T and7T were used for the simulation of the T_(2ρ) measurements performedwith CP^(HS1) versus CP^(HS4) pulse sequences. Taking into accountcontributions due to dipolar relaxations (Eq. 9), agreement was notedbetween theory and the T_(2ρ) measurements with the CP^(HS1) andCP^(HS4) pulse sequences. A ratio ofT_(2ρ)(CP^(HS4))/T_(2ρ)(CP^(HS1))≈1.18 was obtained.

The observed increase of the T_(2ρ)(CP^(HS4)) versus T_(2ρ)(CP^(HS1))cannot be attributed to conventional magnetization transfer (MT),because MT generally causes a reduction in image SI in tissue, which iscontrary to the changes noted. Although a small contribution from apositive Nuclear Overhauser Effect (NOE) associated with the fastmotional regime can lead to an increase in the SI, it cannot becompletely ruled out.

The isochoronous CE mechanism between spins at different sites A and Bwith δω=0 and T_(2A)≠T_(2B) can also lead to a change of the T₂ ^(†)time constants through changes in the apparent populations of the sitesA and B and the time constants T_(2A) and T_(2B) (Eq. 8). Theexperimental results and theoretical analysis suggested that T_(2ρ)contrast generated by HS1 and HS4 pulses is sensitive to the DA in thehuman brain.

Thus, it appears that adiabatic pulses with different modulationfunctions can be exploited to directly assess T_(2ρ) relaxation and togenerate tissue contrast in the human brain. Analysis of the T₂ ^(†)time constants measured using adiabatic CP pulse sequences can take intoaccount both T_(2ρ) relaxation during the adiabatic pulses and therelaxation due to the free precession during the interpulse timeintervals. Modeling based on the anisochronous DA mechanism (in the FXL)alone leads to an impossible dependence of δω on magnetic field. One ormore other relaxation channels must therefore contribute to transverserelaxation during an adiabatic CP pulse sequence. A probablecontribution appears to be relaxation due to dipolar interactions. Fordipolar relaxation between identical spins, the dependence of the T_(2ρ)time constants on the modulation functions of the AFP pulses was foundto be insignificant. Thus, DA is the major mechanism in the brain tissuecontributing to the T_(2ρ) dependence on the modulation functions of AFPpulses.

In addition to T_(2ρ) relaxation, T_(1ρ) contrast can also be generatedby adiabatic HSn pulses in human brain at, for example, a field of 4T.In particular, the present subject matter considers dipolarcross-correlations mechanism in tissue.

For example, during a train of adiabatic full passage (AFP) pulses ofthe HSn family placed prior to the excitation by the adiabatic halfpassage (AHP) pulse, magnetization follows the time-dependent effectivemagnetic field ω_(eff)(t) during the AFP pulses. When the time betweenpulses is zero (or approximately zero), magnetization decay during thepulse train is governed mainly by time-dependent longitudinal relaxationin the tilted double rotating frame, T_(1ρ). T_(1ρ) relaxation issignificantly dependent on the choice of adiabatic pulses with differentmodulation functions. Accordingly, the present subject matter allows forT_(1ρ) relaxation contrast of ¹H₂O in the human brain and measurement ofrelaxation parameters of the dipolar relaxation pathways.

The transverse relaxation in the rotating frame (T_(2ρ)) is the dominantrelaxation mechanism during an adiabatic Carr-Purcell (CP) spin-echopulse sequence with no delays between refocusing pulses.Exchange-induced T_(2ρ)(T_(2ρ,ex)) and the T_(2ρ) due to dipolarinteractions (T_(2ρ,dd)) was found to depend on the modulation functionsof the adiabatic pulses used. This property of adiabatic pulses can beused to generate the T_(2ρ) contrast in the human occipital lobe ¹H₂O at4T magnetic field. It was shown that dynamic averaging (DA), e.g.chemical exchange and diffusion in the locally different magneticsusceptibilities, is the major mechanism contributing to the T_(2ρ)dependence on the modulation functions of the adiabatic full passage(AFP) pulses of the HSn (n=1,4) family in brain tissue.

Consider next the adiabatic T_(1ρ) contrast generated by an adiabatictrain of HS1 and HS4 pulses placed prior to the excitation by theadiabatic half passage (AHP) pulse with no time intervals betweenpulses. Adiabatic T_(1ρ) contrast originates from dipolarcross-correlations (e.g., interference between dipolar relaxationpathways), and the DA mechanism has just a minor contribution to theR_(1ρ) relaxation rate constants in the human brain tissue. AdiabaticT_(1ρ) contrast provides a possibility to directly assess dipolar typeof interactions (i.e., cross-correlations) in living tissue. In general,adiabatic pulses exhibit B₁ insensitivity.

NMR relaxation in tissue is subject to complex mechanisms includingchemical exchange and magnetic interactions between different molecularconstituents in several tissue compartments. A two-site model thatrepresent extracellular (as well as interstitial) and intrasellularwater reservoirs, respectively, was studied. These two reservoirs arecoupled by the two-site exchange (2SX) mechanism that represents waterdiffusion through cell membranes.

In one example, three issues are considered: 1) orientational order of¹H dipolar interactions and its contribution to the relaxationdispersion; 2) the effect of cross-correlations between water protonsand the macromolecules associated protons; 3) 2SX between two waterreservoirs and CE between labile protons (associated withmacromolecules) and water.

FIG. 5A illustrates a schematic representation of the adiabatic pulsesequence used for T_(1ρ) measurements and scaling for the resultsappears in FIG. 5D.

In FIGS. 5B and 5C the T_(1ρ) maps generated from the measurements using(HS1)_(n)−90° pulse (FIG. 5B) and (HS4)_(n)−90° pulse (FIG. 5C) arepresented. As illustrated, T_(1ρ) relaxation is significantly affectedby the modulation functions of the adiabatic pulse used and the ratioT_(1ρ)((HS1)_(n)−90°)/T_(1ρ)((HS1)_(n)−90°)≈1.51±0.15 was obtained (5individuals). The contribution of the anisochronous T_(1ρ,ex) (e.g., CEbetween spins with different chemical shifts dw≠0) during the HS1 andHS4 pulses was estimated using the aforementioned relaxation equationsand the parameters obtained from the 4T human relaxation data. Thisanalysis yields an exchange-induced relaxation rate constants that aresmaller as compared to dipolar relaxation rate constants for therotating frame longitudinal relaxation. This implies that dipolarrelaxation dominates under these experimental conditions (ω₁ ^(max)=2.5kHz, pulse length Tp=3 ms). In this work the formalism for thethree-spin system dipolar relaxations T_(1ρ,dd) was implemented for theHS1 (FIG. 5B) and HS4 (FIG. 5C) pulses, respectively. The dependences ofthe R_(1ρ,dd) on the rotational correlation times τ_(c) during the HS1and HS4 pulse are presented on FIG. 6.

FIG. 5E illustrates the region of interest (ROI) of the T₁ weightedimage and FIG. 5F illustrates T_(1ρ) relaxograms of a human brain imageslice in the occipital lobe, generated from the T_(1ρ) maps.

FIGS. 6A and 6B illustrate calculated longitudinal relaxation rateconstants (R_(1ρ)) during the HS1 pulses (6A) and HS₄ pulses (6B) as afunction of the rotational correlation time (τ_(c)). The pulseparameters used for calculation were: pulse length Tp=0.003s, R=20,ω₁=2.5 kHz.

FIGS. 7A and 7B illustrate the rotating frame of reference. Inparticular, FIG. 7A illustrates the effect of an adiabatic full-passageon a magnetization vector initially in the transverse plane, as viewedfrom the frequency modulated reference frame denoted by x′, y′ and z′.During adiabatic rotation, the magnetization vector M remainsapproximately perpendicular to ω_(eff)(t). The figure also illustratesthe orientation of the tilted double rotating frame (TDRF), denoted byx″, y″ and z″, relative to the frequency modulated frame. Any componentof M that is aligned with ω_(eff)(t) will relax with time constantT_(1ρ)(t) along the z″ axis whereas the component perpendicular toω_(eff)(t) will relax with the time constant T_(2ρ)(t) in the x″-y″plane. FIG. 7B illustrates a vector diagram showing the effective fieldE(t) and its components in the TDRF. Vector M evolves around E(t) in aplane tilted by the angle ε(t) relative to the x″-y″ plane. When theadiabatic condition is satisfied, |ω_(eff)(t)|>>|dα/dt|, the fieldcomponent dα/dt can be neglected and vector M revolves aroundω_(eff)(t).

FIGS. 8A and 8B illustrate amplitude (8A) and frequency (8B) modulationfunctions in the frequency modulated frame for two different adiabaticfull passage pulses, namely HS1 and HS4.

FIG. 9 illustrates theoretical comparison between relaxation R_(2,ex),R_(2ρ,ex) R_(1ρ,ex) during adiabatic pulses HS1 and HS4 based on ω₁^(max)/2π=2.5 kHz, δω=0.85 ppm and P_(A)P_(B)=0.247.

Adiabatic T_(1ρ) contrast based on the difference in the modulationfunctions of the adiabatic pulses, was generated in the human brain.This relaxation contrast provide a direct assessment of the dipolarrelaxations in tissue. Adiabatic T_(1ρ) contrast may facilitateinvestigation, characterization and diagnosis of neurodegenerativedisorders, cancer and stroke.

FIG. 10 illustrates a block diagram of exemplary magnetic resonancesystem 100. System 100 includes signal generator 120 coupled toprocessor 130. The signal generator provides radio frequency pulses tomagnetic resonance transmitter coil 110 within magnetic resonance system100. Processor 130 executes instructions that controls the operation ofsignal generator 120. In one example, the instructions are tailored toform a sequence including a pulse train and an excitation pulse. Thepulse train, in one example, includes a plurality of pulses, at leastone pulse of which satisfies the adiabatic condition. The sequence isconfigured to generate a magnetic resonance signal that decays byrelaxing in a rotating frame of reference. Adiabatic pulses in the pulsetrain are characterized by different modulation functions, e.g. aremodulated in amplitude or waveform (phase and frequency). For example,an interpulse interval between adjacent pulses can be substantially zeroor non-zero. The order of the adiabatic pulse train and the excitationpulse can be tailored for a particular purpose, including for example,analysis of T_(1ρ) or T_(2ρ) relaxation. In one example, at least oneslice selection pulse is applied to the region of interest. In oneexample, controller 140 is coupled to processor 130 and controller 140is configured to receive a user selection. For example, controller 140can include a keyboard, a touch-screen, a mouse or other user-operablecontrol device and the sequence is configured based on an input receivedby controller 140. For instance, a selection received by controller 140is used to select a modulation function for the sequence or a relaxationparameter. In one example, system 100 includes receiving coil 160coupled to output device 170. Output device 170 can include, forexample, a display, a printer, a storage device, or other component togenerate or display data based on the magnetic resonance signal.Transmit coil 110 and receive coil 160 are disposed proximate to regionof interest 150.

FIG. 11 illustrates an exemplary method according to the present subjectmatter. In the figure, method 200 includes sequentially applying a pulsetrain and an excitation pulse (at 210) and generating data based on amagnetic resonance signal received (at 220) from a region of interestand wherein the data corresponds to relaxation (at 230) in a rotatingframe of reference. The pulse train and the excitation pulse are appliedto the region of interest in a static magnetic field. The pulse trainincludes a plurality of pulses, each having duration and a waveform andwherein the waveform is configured to modulate an effective field vectorand wherein the relaxation is based on the waveform. Different pulses ofthe plurality of pulses can differ in terms of the pulse duration orwaveform. A second pulse train can be applied wherein the second pulsetrain is modulated in a manner different than the first pulse train andthe relaxation is determined based on the different magnetic resonancesignals received. The pulse train includes an adiabatic full passagepulse and the excitation pulse can include an adiabatic half passagepulse. The order of the pulse train and the excitation pulse can beselected to analyze a different relaxation parameter. Slice selectionpulses can be applied before, during or after the pulse train and theexcitation pulse. Data can be received simultaneously with applicationof the slice selection pulse. The resulting data can include a visualimage, spectroscopy data or both.

In one example, a method includes applying a pulse sequence (includingan adiabatic pulse train and an excitation pulse) to a specimen,receiving a magnetic resonant image from the specimen and determiningrelaxation based on the signal. As noted elsewhere in this document, theorder of the pulse train and the excitation pulse are tailored for aparticular relaxation. A number of relaxation mechanisms can be studiedwith the present subject matter and one example includes selecting oneor more mechanisms from a plurality of mechanisms and the sequence istailored based on the selected mechanism. The sequence can be configuredin terms of pulse order, modulation function, pulse duration and powerlevel (amplitude). In one example, the adiabatic pulse train includes aplurality of adiabatic full passage pulses and the excitation pulseincludes an adiabatic half passage pulse.

The term contrast denotes a difference. In the context of magneticresonance spectroscopy, contrast refers to a perceivable difference inproperties that makes a feature of an image distinguishable from otherfeatures, including, for example, a background. By way of example, in astroke patient, contrast between carotid arteries and plaque allowsdetection, identification and determination of progression of diseaseformation.

In one example, relaxation is measured during an adiabatic pulse withtime-dependent RF radiation. The RF radiation is modulated to generatedifferent functions. Relaxation mechanism can be selectively assessedbased on the design of the pulse sequence applied. For example, thepulse train can be followed by an excitation pulse for analysis ofT_(1ρ) and the order reversed for analysis of T_(2ρ) relaxation.Furthermore, the RF radiation can be tailored, in terms of the amplitudeand waveform (phase and frequency) to achieve different purposes. Inparticular, the different relaxation mechanisms can be discerned bysuitable modulation and tailoring of the pulse sequence using adiabaticpulses as well as non-adiabatic pulses. In one example, relaxation ismeasured during an adiabatic full passage pulse train.

In one example, data regarding isochronous exchange, or dipole-dipoleinteraction, is generated based on T_(1ρ) as function of time. In oneexample, data regarding anisochronous exchange is generated based onT_(2ρ) as function of time. In one example, anisochronous exchangecorrelates to a difference in pH.

In one example, the sequence includes applying an adiabatic pulse at aradio frequency and aligned on an axis different than that of the staticmagnetic field. Magnetic resonance data corresponding to relaxation timeis generated based on a signal received by a receiving coil. In oneexample, the relaxation time is viewed in frame of reference rotating ina plane lying substantially perpendicular to the first axis. Contrastcan be generated based on difference data corresponding to a first andsecond pulse sequence. The pulse sequences can be modulated in amplitudeand frequency. In one example, a delay period between adjacent pulses ofthe pulse sequence is configured to produce a desired result. Relaxationtime can be determined in a rotating frame that is aligned transverselyor longitudinally.

Alternative Examples

Other examples, in addition to those specifically described above, arealso contemplated. For example, one or more radio frequency pulses ofthe pulse train can be modulated to yield a particular relaxation rateconstant. For instance, the duration or amplitude of the waveform ofindividual pulses in the pulse train can be modulated to obtain aparticular relaxation. By modulating the amplitude, frequency and phaseof the pulse train, the observable relaxation rate in the rotating frameof reference can be modulated.

In one example, one or more pulses of the pulse train satisfy theadiabatic condition sometimes expressed as |ω_(eff)(t)|>>|dα/dt|. In oneexample, one or more pulses of the pulse train are non-adiabatic pulses.

In one example, the train has no interpulse interval between adjacentpulses. In one example, a brief interpulse interval separates adjacentpulses of the pulse train.

In one example, multiple runs are executed for a particular specimen ina region of interest with each run including a particular pulse trainand excitation pulse. The pulses of the different pulse trains caninclude frequency modulated, amplitude modulated or phase modulatedpulses configured for a particular relaxation with each train havingdifferent modulation or each pulse within a train having differentmodulation.

One example of the present subject matter includes a method forgenerating a contrast for magnetic resonance spectroscopy (T_(2ρ) andT_(1ρ)) based on modulating a function that defines the shapes of thepulses in a pulse train. The shapes (trajectory) of the pulses aretailored or modulated to increase persistence of a received signal andto enhance sensitivity.

In one example, the pulse train includes adiabatic pulses or otherpulses that sweep as a function of time. By modulating the pulse, thepresent subject matter allows modulating of the contribution arisingfrom exchange and dipole-dipole interaction. The pulse can be modulatedin terms of the amplitude of the radio frequency and the frequency(phase). In addition, a time delay or interval can be adjusted.

For example, in a sample of ethanol and water (an OH group), thechemical exchange is fast (the system is in the fast exchange regime)and a spectrum reveals a single resonance at the frequency of water. Bychanging the adiabatic pulse modulation the relaxation rate constant canbe modulated. Relaxation rate constants measured at different pH levelswere measured with the different pulses of the hyperbolic secant (HSn)family and described well by the theory that was derived.

The pulse sequence can be modulated by changing the number of pulses(increasing or decreasing), changing a delay time period (insert, removeor adjust a time period) and changing the pulse modulation function(amplitude, frequency or phase).

The underlying processes for T₁ and T₂ differ. One factor contributingto T₁ is dipole-dipole interactions. The nucleus of a water molecule hasa magnetic dipole which can convey energy to other molecules (each alsohaving magnetic dipoles) that are tumbling at particular frequencies inthe RF range. Dipole-dipole interactions are similar to transitions inenergy levels. After exposing the sample to RF excitation, the magneticdipoles of the particular water molecule and the neighboring dipolestumble and release energy as they resume alignment with the magneticfield.

The T₂ process occurs by dipole-dipole interactions and by othermechanisms, including dynamic averaging. Dynamic averaging includeschemical exchange and diffusion. Chemical exchange refers to theexchange of protons in a water molecule with protons in other nearbywater molecules. For example, water molecule has hydrogen atoms that arechemically exchanging with other hydrogens, such as hydroxel groups onon DNA, macromolecules, enzymes, membranes, or other large molecules.Dynamic averaging leads to a dephasing. The magnetic susceptibility of atumor, a blood vessel and brain tissue all give rise to different localmagnetic field variations. The spins in the different tissue willprecess at different frequencies based on the local field strengthwithin the tissue. Thus, the magnetic resonance relaxation parameterswill be different. Other lesser factors in addition to dynamicaveraging, such as dipolar relaxation pathways, also contribute to T₂relaxation. The cross relaxations and the relaxations due to chemicalshift anisotropy are believed to be less significant than the auto(self)-relaxations and the dynamic averaging.

In one example, a magnetic resonance image is generated by acquiring asignal following excitation. For example, an excitation pulse is appliedand after some time delay (called the echo time or TE), the signal isacquired. In the case of a 180 degree excitation pulse, the acquiredsignal is referred to as a spin echo.

During the time delay, chemical exchange, diffusion and other processwill have caused the signal to decay. If detected early, the signal willhave a greater magnitude and after a delay, the signal intensity will belower.

The amount of signal decay depends on the environment of the watermolecule as well as the types of macro molecules or type of membranes.For example, in cancers, the process of signal decay is catalyzed by pH.Cancers have a relatively acidic extracellular pH.

Both relaxation times T₁ and T₂ are a function of the chemical exchangeprocess. In addition, time T₁ is also a function of dipole-dipoleinteraction.

In the present subject matter, the signal is received in conjunctionwith the application of a continuous series of excitation pulses. It isbelieved that continuous application of pulses can suppress certaincontribution and thus, avoid decay of the signal.

To achieve this result, the excitation pulses are modulated in aparticular manner. In one example, the frequency of the pulses aremodulated and can be described as adiabatic full passage.

In one example, decay can be suppressed completely or suppressed to aselected degree based on the modulation of the excitation pulses. Forinstance, two images can be acquired using different pulse trains, witheach train having different pulse shapes, frequency or modulation. Adifference image based on the different pulse trains can reveal thecontribution from, for example, chemical exchange only.

In one example, the present subject matter allows separation of the twocontributions (chemical exchange and dipole-dipole interaction) in a T₂image.

In one example, the contrast can be made specific to a particular pH andthus allow imaging or spectroscopy of, for example, a tumor having anacidic extracellular pH.

The present subject matter reduces the masking effect of the chemicalexchange process caused by dipole-dipole interaction, thus allowing animage based on different pH values. For example, a disease or conditionthat produces a change in the dipole-dipole interaction in one directioncan be obscured by a chemical exchange in the opposite direction.

At high magnetic field strength, the magnetic resonance image isdominated by the exchange contribution. The difference in resonancefrequency (when the hydrogen is in different positions) changes linearlywith the magnetic field. With a larger chemical shift difference, thedephasing process occurs more rapidly, thus yielding a bigger differencein frequency. Chemical exchange is a more dominating effect as magneticfield strength rises. For example, at a magnetic field of 4T chemicalexchange is dominant. As to dipole-dipole interaction, there is littledependence on magnetic field strength. At lower fields, the relativemagnitude of dipole-dipole interaction is comparable to that of chemicalexchange.

In addition to generating changes in the exchange contribution,selection of the pulse train shape can also generate changes in thedipole-dipole contribution.

The pulse train shape can be selected to modulate the contribution torelaxation arising from chemical exchange and to modulate thecontribution to relaxation arising from dipole-dipole interaction.

In one example, the radio frequency excitation pulse can be selected tokeep the chemical exchange process focused and thus prevent dephasing ofthe magnetization.

The term T_(2ρ) corresponds to a radio frequency pulse applied in therotating frame and at the same frequency as the spins precess.Magnetization dephases (phase coherence is lost) because of the exchangeprocess, dipole-dipole interaction and B1 inhomogeneity. The inabilityto, for example, provide a perfectly homogenous RF field causes the rateat which the spins evolve to vary and since the effective B1 field isvarying, then phase coherence will also vary.

The present subject matter includes a particular sort of pulse sequenceto achieve T_(2ρ) contrast. The shapes of the pulses are changed tomodulate the contrast.

In one example, a continuous RF pulse train or sequence (with one pulsefollowing another) and having a frequency dependence (including, forexample, those having frequency swept pulses, or adiabatic fullpassage). In an adiabatic full passage pulse, the frequency of the RFsweeps from one side of resonance to the other side of resonance.

The present subject matter allows for extended excitation of the sampleand thus permits gathering of more information (improved signal to noiseratio) and faster image generation. The time dependence of the effectivefield sweep determines the relaxation rate constants caused by thedifferent relaxation mechanisms.

The rate constant for laboratory frame longitudinal relaxation (R₁) isparticularly sensitive to the molecular fluctuations of magnetic dipolarinteractions, but only those at high frequencies near that (ω₀) of theLarmor precession (i.e., in the MHz range). It is believed that dipolarfluctuations in tissue occur at lower frequencies (i.e., in the kHzrange). The rotating frame longitudinal relaxation rate constant(R_(1ρ)) is driven principally by dipolar fluctuations at frequenciesnear that (ω_(eff)) of the effective Larmor precession in thesimultaneous presence of the RF and laboratory magnetic fields. Sincethis can be “tuned” by adjustment of ω₁, the (Rabi) frequency measure ofthe RF amplitude, it is believed that this can provide experimentalaccess to the relevant lower frequencies by modulating the pulse train,the present subject matter allows selection of the molecular motionsthat contribute to relaxation. For example, the motions occurringbetween water and large molecules instead of water and intermediate sizemolecules can be isolated since larger molecules tumble more slowly. Inother words, the dipole-dipole relaxation contribution for MR contrastcan be modulated based on the pulse train modulation function selected.

In one example, a difference image is generated by subtracting imagesacquired by different modulation functions and normalizing.

For example, two images are acquired using adiabatic full passage pulsetrains based on HS4 and HS1. The difference of these two images is thennormalized by one of the images to generate a difference image whichexhibits contrast. For instance, a bright region in the difference imagecorresponds to a larger difference which may indicate a more dynamicaveraging and dark regions may indicate CSF which exhibits low levels ofdynamic averaging and thus low sensitivity to the type of pulse appliedin the pulse train.

The present subject matter provides a contrast for MR imaging andprovides a method and system to increase the persistence of the signalas well as enhance sensitivity because the signal decays more slowly.Detection and identification of progression of diseases such as breastcancer, brain tumor and stroke detection and plaque formation areexemplary applications for the present subject matter.

In one example, both the B₁ field and the radio frequency sweep is afunction of time. By modulating the pulse, the contribution torelaxation can be modulated. For instance, pulse modulation allowsmodulation of the exchange and the dipole contributions. The pulses ofthe pulse train can be modulated in many ways including phase, frequencyand amplitude.

For example, by changing the amplitude of the radio frequency pulse, therelaxation process reveals sensitivity to changes in pH level. Such amechanism for contrast using MR imaging may be useful for detection ofcancerous cells since cancer cells typically have a low extracellular pHand benign tumors don't have an acidic extracellular pH.

In one example, plaque can be distinguished from other tissue byconfiguring the pulse sequence in terms of pulse length, peak power,pulse modulation function and inter-pulse time interval. As anotherexample, a particular body part or tissue can be examined by suitablyconfiguring the pulse sequence. The relaxation is measured during theradio frequency adiabatic pulse wherein the pulse is modulated overtime.

It is to be understood that the above description is intended to beillustrative, and not restrictive. For example, the above-describedembodiments (and/or aspects thereof) may be used in combination witheach other. Many other embodiments will be apparent to those of skill inthe art upon reviewing the above description. The scope of the inventionshould, therefore, be determined with reference to the appended claims,along with the full scope of equivalents to which such claims areentitled. In the appended claims, the terms “including” and “in which”are used as the plain-English equivalents of the respective terms“comprising” and “wherein.” Also, in the following claims, the terms“including” and “comprising” are open-ended, that is, a system, device,article, or process that includes elements in addition to those listedafter such a term in a claim are still deemed to fall within the scopeof that claim. Moreover, in the following claims, the terms “first,”“second,” and “third,” etc. are used merely as labels, and are notintended to impose numerical requirements on their objects.

The Abstract of the Disclosure is provided to comply with 37 C.F.R.§1.72(b), requiring an abstract that will allow the reader to quicklyascertain the nature of the technical disclosure. It is submitted withthe understanding that it will not be used to interpret or limit thescope or meaning of the claims. In addition, in the foregoing DetailedDescription, various features may be grouped together to streamline thedisclosure. This method of disclosure is not to be interpreted asreflecting an intention that the claimed embodiments require morefeatures than are expressly recited in each claim. Rather, as thefollowing claims reflect, inventive subject matter may lie in less thanall features of a single disclosed embodiment. Thus, the followingclaims are hereby incorporated into the Detailed Description, with eachclaim standing on its own as a separate embodiment.

1. A system comprising: a signal generator configured to couple with amagnetic resonance transmitter coil; and a processor configured toexecute instructions to control the signal generator, the instructionsincluding forming a sequence having an adiabatic pulse train and anexcitation pulse, the sequence configured to generate a magneticresonance signal that decays by relaxing in a rotating frame ofreference.
 2. The system of claim 1 wherein the adiabatic pulse trainincludes a plurality of pulses, at least one of which satisfies anadiabatic condition and having a duration and a waveform.
 3. The systemof claim 2 wherein the duration of at least two pulses of the pluralityof pulses are different.
 4. The system of claim 2 wherein the waveformof at least two pulses of the adiabatic pulse train are different. 5.The system of claim 1 wherein an interpulse interval between two pulsesof the adiabatic pulse train is substantially zero.
 6. The system ofclaim 1 wherein the instructions including applying the adiabatic pulsetrain before applying the excitation pulse.
 7. The system of claim 1wherein the instructions including applying the excitation pulse beforeapplying the adiabatic pulse train.
 8. The system of claim 1 wherein theinstructions including generating and applying a slice selection pulse.9. The system of claim 1 further including a controller coupled to theprocessor, the controller configured to receive a user selection. 10.The system of claim 9 wherein the controller is configured to receive aselection as to a modulation function for the sequence.
 11. The systemof claim 9 wherein the controller is configured to receive a selectionas to a relaxation parameter, wherein the sequence is configured as afunction of the selected relaxation parameter.
 12. The system of claim 1further including: a receiving coil; and an output device coupled to thereceiving coil, the output device configured to display data based onthe magnetic resonance signal.
 13. A method comprising: sequentiallyapplying an adiabatic first pulse train and an excitation pulse to aregion of interest in a static magnetic field, the first pulse trainhaving a plurality of pulses each of which has a pulse duration and awaveform wherein the waveform is configured to produce a modulatedeffective field vector; and generating data based on a magnetic resonantsignal received from the region of interest, the data corresponding torelaxation in a rotating frame of reference, the relaxation based on thewaveform.
 14. The method of claim 13 wherein a pulse duration of a firstpulse of the plurality of pulses differs from a pulse duration of asecond pulse of the plurality of pulses.
 15. The method of claim 13wherein a waveform of a first pulse of the plurality of pulses differsfrom a waveform of a second pulse of the plurality of pulses.
 16. Themethod of claim 13 further including sequentially applying a secondpulse train to the region of interest, the second pulse train having aplurality of pulses each of which has a pulse duration and a waveformwherein the waveform is configured to produce a modulated effectivefield vector, and wherein the second pulse train differs from the firstpulse train.
 17. The method of claim 13 wherein the first pulse trainincludes an adiabatic full passage pulse.
 18. The method of claim 13wherein the excitation pulse includes an adiabatic half passage pulse.19. The method of claim 13 wherein the first pulse train is appliedbefore the excitation pulse.
 20. The method of claim 13 wherein theexcitation pulse is applied before the first pulse train.
 21. The methodof claim 13 further including applying at least one slice selectionpulse.
 22. The method of claim 21 wherein generating data includessimultaneously receiving the signal and applying the at least one sliceselection pulse.
 23. The method of claim 13 wherein generating dataincludes at least one of forming an image and forming spectroscopy data.24. A method comprising: applying a pulse sequence to a specimen, thepulse sequence including an adiabatic pulse train and an excitationpulse, the adiabatic pulse train having a plurality of pulses; receivinga magnetically resonant excited signal from the specimen; that decays byrelaxing in a rotating frame of reference and determining a measure ofrelaxation based on the signal.
 25. The method of claim 24 wherein thesequence includes the adiabatic pulse train followed by the excitationpulse.
 26. The method of claim 24 wherein the sequence includes theexcitation pulse followed by the adiabatic pulse train.
 27. The methodof claim 24 further including: selecting a relaxation mechanism from aplurality of mechanisms; and configuring the sequence based on theselected relaxation mechanism.
 28. The method of claim 27 whereinconfiguring the sequence includes at least one of selecting an order forthe adiabatic pulse train and the excitation pulse, selecting amodulation function for the adiabatic pulse train, selecting amodulation function for the excitation pulse, selecting a pulseduration, and selecting a pulse power level.
 29. The method of claim 24wherein the adiabatic pulse train includes a plurality of adiabatic fullpassage pulses.
 30. The method of claim 24 wherein the excitation pulseincludes an adiabatic half passage pulse.